Professional Documents
Culture Documents
Fall, 2011
FINAL EXAMINATION KEY
1:30 PM, January 18TH, 2012
Duration: 20 minutes reading and then 3.0 hr to write
Name_____KEY______________________________________________________
(Official Name)
This is an open book examination; you may use anything that is not alive or connected to the Web.
Note: if you do not know the complete or specific answer, give a partial or general answer
We love to give partial credit.
If there seems to be more than one good answer, explain your thinking.
If you invoke resonance delocalization as part of your answer, draw the relevant resonance structures.
If you draw a chair cyclohexane, be sure to orient the bonds carefully.
If you do not know a structure and need to write a mechanism, write a general mechanism for partial credit.
You need not draw transition states as part of a mechanism unless expressly instructed to do so.
USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS. SHOW ALL INTERMEDIATES.
BE SURE TO INCLUDE ALL FORMAL CHARGES.
Write only in the space provided for each question.
Score:
p2___________/ 10
p3___________/ 10
p4___________/ 18
p5___________/ 18
p6___________/ 15
p7___________/ 12
p8___________/ 6
p9___________/ 14
p10__________/ 10
p11__________/ 12
p12__________/ 15
p13__________/ 14
p14__________/ 30
p15__________/ 16
Lecture Total:
/200
There are 19 pages in this exam; please check now to be sure you have a complete set. The last page is Table 3.2 from the
text related cyclohexane conformational data, and a glossary of definitions.
Pledge:_________________________________________________________________________________
1. Fumaric acid is an intermediate in the Krebs cycle and is involved in the production of energy in the form of ATP from
the breakdown of carbohydrates, fats, and proteins. Fumaric acid and its closely related isomer maleic acid have several
unique properties that significantly alter their relative properties in living organisms and in the laboratory. For example,
consider the aqueous pKa values for the two compounds.
HO2C
HO2C
CO2H
CO2H
fumaric acid
maleic acid
pKa1: 3.02
pKa2: 4.38
pKa1: 1.92
pKa2: 6.23
(a) (5 pts) Provide the single best reason why the most acidic proton (pKa1) on maleic acid is approximately 12.5 times
more acidic than the corresponding proton on fumaric acid.
HO2C
HO2C
CO2H
CO2
O
HO2C
CO2H
H O
(b) (5 pts) Interestingly, the second proton to be deprotonated on maleic acid (pKa2) is approximately 70 times less acidic
than the corresponding second proton on fumaric acid. Provide the single best reason to explain this data.
O2C
HO2C
CO2
CO2
O
O
H O
maleic acid: 1 pt for stabilization of acid by H-bond; 3 pts for dipole-dipole destabilization of conjugate
base
fumaric acid: 1 pt for dipole-dipole stabilization of conjugate base
2. (5 pts) (a) Label the following molecules in order of basicity (most, least, intermediate), and defend your choice. You must draw
pictures to receive credit.
O2N
Me
MeO
NMe2
NMe2
intermediate
NMe2
least
O
N
most
O
N
NMe2
O
N
NMe2
Me
NMe2
Me
NMe2
NMe2
MeO
MeO
destabilized due to electron-electron repulsion
NMe2
NMe2
O2N
NMe2
t-Bu
O2N
NMe2
t-Bu
O2N
x NMe2
t-Bu
O2N
3. (18 pts) For each of the following pairs of reactions, (i) draw the product(s) of each reaction and (ii) circle which
member of the pair would be FASTER. (iii) Explain briefly the most important reason for your choice.
O
(a)
Me
Me
EtOH
Me
Me
Me
AgNO3
Br
Me
Me
Me
Me
Me
EtOH
Me
Me
AgNO3
Br
OEt
Me
Me
Me
Me
Me
OEt
Me
Me
Me
(b)
NaI
t-Bu
Cl
acetone
Cl
t-Bu
Cl
t-Bu
t-Bu
H
I
NaI
t-Bu
Cl
acetone
t-Bu
t-Bu
Cl
t-Bu
Cl
!
(c)
HO
NaH
Br
Et2O
(0.1M)
Me
OH
NaH
Me
Br
Et2O
(0.1M)
Me
Me
1. BH3, Et2O
D: C11H14O
E: C11H14O
H2SO4
Ph
2. H2O2, NaOH
select IR data:
3432, 3083, 1644,
1610 (phenyl) cm1
H2O
C
(a) (6 pts) Predict the structure of D and draw the best mechanism for step (1) of its formation. Include a carefully
rendered drawing of the rate-determining transition state of the reaction.
Ph
BH3
H2B
! H
H2B
!
H
Ph
H2O2/NaOH
Ph
HO
H2B
Ph
H
Ph
Ph
B
H
Ph
D
Ph
Ph
Ph
H
H+
Ph
H2O
formation of stabilized
benzylic cation is favorable
even though it is still
secondary
Ph
OH
H2O
3 pts for correct structure of E (1 pt for wrong structure but consistent with IR data)
1 pt for Markovnikoff protonation
1 pt for cyclopropane ring opening
1 pt for cleavage of correct cyclopropane bond
1 pt for water addition to cation
1 pt for deprotonation of oxonium
(no penalty for showing E or Z alkene isomer)
(c) (4 pts) Compounds D and E were both treated with MnO2, but only one of the two underwent reaction. Predict which
compound reacted with MnO2; draw the structure of the resulting product; and briefly rationalize your choice.
H
Ph
O
Compound E will react with MnO2:
MnO2 only oxidizes allylic or benzylic alcohols because it is a mild oxidant. E contains a benzylic alcohol whereas D
contains an aliphatic alcohol.
5. Consider the following reaction in the gas phase and the provided data:
Me
Me
Cl
F
Me
N
Me
Me
NMe3
Cl
Cl
Me
Me
LUMO: !* CCl
(f) (12 pts) On one plot, draw reaction coordinate diagrams for the gas phase and aqueous reactions. Be sure that your
diagrams account for the relative energies of the starting materials, products, and activation energies between the two
conditions. Label "Gogas, "Ggas, "Goaq and "Gaq.
TSgas
!G aq < !G gas
potential energy
!G gas
TSaq
!G aq
!Gogas >0
F + NMe3
(gas)
F + NMe3
(H2O)
!Goaq < 0
G + Cl
(gas)
G + Cl
(H2O)
reaction coordinate
1 pt for single TS (SN2) for both reactions
1 pt for correct identification of activation energy ("G)
1 pt for correct identification of free energy ("Go)
1 pt for aq starting materials lower energy than gas phase starting materials
1 pt for aq products lower energy than gas phase products
1 pt for aq transition state lower energy than gas phase transition state
2 pts for "Gogas > 0 as given
2 pts for "Goaq less than "Gogas (probably negative - part (e))
2 pts for "Gaq < "Ggas transition state stabilization more significant than starting material stabilization.
Me
Me
NaOEt
(i)
Br
Me
EtOH
Me
Me
Me
100%
Me
Me
Me
0%
Me
Me
NaOEt
(ii)
Br
Me
EtOH
Me
Me
Me
25%
Me
Me
75%
Br
Me
Me
OEt
H
Me
NaOEt
+ HOEt + NaBr
EtOH
Me
Me
(c) (12 pts) Draw the chair conformations of H and of I (4 total). Circle the lowest energy chair conformation for each
molecule and calculate how much lower in energy each is relative to the higher energy form (note: the back page of the
exam has useful data for doing this). Show your work and if necessary, identify any ambiguities in your estimate.
i-Pr
axial i-Pr: + 2.1 kcal/mol
axial Br: + 0.5 kcal/mol
axial Me: + 1.7 kcal/mol
1,3 diaxial Br/Me interaction
+ 4.3 kcal/mol
Me
i-Pr
Br
Br
Me
i-Pr
Br
i-Pr
Me
Br
Me
+3.3 kcal/mol
(d) (2 pts) Why does reaction (i) give only one product? Explain your answer using 3-dimensional pictures.
i-Pr
H
Me
i-Pr
H
H
Br
Br
Me
10
H
Br
(e) (4 pts) Why does reaction (ii) favor the indicated product? Explain your answer using 3-dimensional pictures.
Me Br
Br
Me
i-Pr
H
Me
H
Elimination will occur from the low energy chair conformation. Two axial C-H bonds are aligned antiperiplanar to
the C-Br bond and could undergo elimination. Elimination to favor the more stable/more-substituted double bond
is faster because the transition state leading to its formation is lower in energy.
1 pt for E2 from correct chair conformation
2 pts for identifying both antiperiplanar beta C-H bonds
1 pt for more substituted double bond, more stable = lower energy transition state
(f) (6 pts) Assign the 1H NMR spectra below to the two products of reactions (i) and (ii). Describe one diagnostic feature
of the spectra that justifies your answer.
Med
Mec
Hc
Hb
Mec
Hb/Hc
Med
Me
He c
He
PPM
Mea
Meb
Meb
Ha
Mea
Ha
6
possible answers:
Me
Hd a
3
PPM
Hd
2
vinyl C-H bond (Ha) is a triplet in the bottom spectra, consistent with the trisubstituted
alkene product and not the disubstituted alkene (Hb/Hc).
Hd is more downfield in the bottom structure, consistent with it being allylic whereas He is
not.
11
7. In 1990 the Sharpless lab at MIT devised an elegant synthesis of L-hexose derivatives beginning from the allylic
alcohol J shown below.
(a) (4 pts) Draw the product (K) of epoxidation of J with mCPBA and indicate how many stereoisomers are possible for
the product.
Me
Me
Me
Me
mCPBA
OH
(+/)-J
OH
Me
Me
Me
Me
Me
O
OH
Me
OH
OH
NaSPh
K
Me
NaOH
H2O, t-BuOH
OH
SPh
OH
L
Me
O
OH
Me
O
Me
O
Me
Me
O
O
O
Me
Me
O
Me
O
OH
O
HO H
Me
O
Me
Me
OH
SPh
OH
L
12
SPh
Me
O
O
OH
H OH
SPh
NaOH
I
1. O3
acetone
formula: C10H18O
2. H2O2
M
H
one step
(next semester)
(a) (4 pts) Draw the structure of N and describe the two most diagnostic features of N that would show up in an IR
spectrum (not the fingerprint region).
SN2
C=C stretch: 1500-1650 cm-1
O-H stretch: broad peak at ~3200-3500 cm-1
=C-H stretch: 3150-3100 cm-1
OH
2 pts for correct structure (1 pt for wrong structure consistent with molecular formula or wrong stereochem)
2 pts for IR peaks (1 each) (consistent with proposed structure)
(b) (4 pts) Draw the structure of O. About where would you expect the most downfield (highest ppm) signal to be in the
1
H NMR spectrum of O?
OH
ozonolysis followed by oxidative workup
OH
(d) (5 pts) Draw the structure of P in its lowest energy chair form (make sure that you draw the correct enantiomer of P).
H
13
9. Labeling molecules with unnatural isotopes can change their spectral properties. Consider the following pair of
molecules, one of which has ONLY 12C carbons (Q), and the other of which has TWO 13C labeled carbons (R) and ONE
12
C carbon.
Br
Br
12C
H3
12C
13C
H
12C
H3
12C
H
13C
H
R
(a) (6 pts) If the molecular ion of Q is set to 100% in the mass spectrum, what percentage is M+1 for Q? M+2? Would
the mass spectrum be different in a predictable way in R? If so, how?
Q
M = 120 (100%)
M+1 (0%)
M+2 (100%)
R
M = 122 (100%)
M+1 (0%)
M+2 (100%)
R
Because frequency is proportional (Mr)-1/2, where Mr is reduced
mass, C=C stretch will decrease in frequency.
Cy
CxH3
Cz
H
(c) (4 pts) How many signals would you observe in the proton-decoupled 13C NMR spectrum for Q? What splitting
patterns would they have and why? How many signals would you observe in the proton-decoupled 13C NMR spectrum
for R? What splitting patterns would they have and why?
Q
None! There are no 13C's
R
Two. Cy and Cz are both doublets (they couple to each other), and CX is 12C
14
10. (30 pts) Provide the necessary reagents to convert 1-methylcyclohexene (S) into the target compounds TY. (Hint:
More than one step may be required in some of the conversions.)
5 pts each 2/5 points for correct connectivity and wrong stereochemistry
3 points for correct first step and wrong second step
Me
Me OH
Br2/H2O
Br
(a)
T (racemic)
S
Me Br
(b)
OH
1. m-CPBA
2. HBr
U (racemic)
1. BH3
2. H2O2/NaOH
(c)
Me
OCH3
S
3. NaH
4. CH3I
V (racemic)
Me OH
OH
1. m-CPBA
(d)
S
2.NaOH/H2O
W (racemic)
Me OH
OH
1. OsO4
(e)
S
2. NaHSO3/H2O
X (racemic)
(f)
1. BH3
2. H2O2/NaOH
Me
O
15
16
11. Caryophyllene is obtained from the oil of cloves. When it is treated with aqueous acid, two products are obtained,
caryolanol and clovene.
Me H
Me
Me H
Me
H2SO4
Me
H
H2O
Me Me H
Me
Me
H
HO
caryophyllene
caryolanol
clovene
(a) (8 pts) Draw the best arrow-pushing mechanism for the formation of caryolanol (you do not need to account for the
stereochemical outcome of the reaction).
Me H
Me
Me
Me H
Me
H
H
H
H
Me H
Me
Me
Me
H
HO
H+
Me H
Me
H2O
Me
OH2
Intermediate
Me H
Me
Me
H
HO
caryolanol
Me Me H
Me Me H
Me
H
H2O
Me
Me
Intermediate
clovene
although this is also a
secondary cation, it is more
stable than the intermediate
because the ring strain in the
4-membered ring has been
relieved
17
+ H+
+ H+
PyHBr3
1
3
CH2Cl2
0 C
PyHBr3
4
CH2Cl2
0 C
Proton-decoupled 13C NMR spectra of butene isomers 1 and 2 and the 1H NMR spectra of dibromides 3 and 4 are
summarized below:
Butene 1
proton-decoupled 13C NMR (CDCl3): d 25.8, 112.1, 141.8
Butene 2
proton-decoupled 13C NMR (CDCl3): d 14.0, 26.7, 116.4, 134.3
Dibromide 3
1
Dibromide 4
1
H NMR (CDCl3): d 1.08 (t, J = 7 Hz, 3H), 1.75-1.91 (m, 1H), 2.12-2.26 (m, 1H),
3.63 (t, J = 10 Hz, 1H), 3.84 (dd, J = 10 Hz, J = 4.5 Hz, 1H),
4.10-4.20 (m, 1H)
(a) (4 pts) Deduce the structures of butene isomers 1 and 2. Indicate how the proton-decoupled 13C NMR spectra of
butenes 1 and 2 support your structural assignments. (Hint: There are only four possible butene isomers. Draw the
four possible isomers.)
There are only four possible butene isomers, A-D. We can use the proton-decoupled 13C NMR spectral data to
differentiate these four isomers. From symmetry considerations alone, we can differentiate 1-butene (A) [4 unique
carbons] and isobutylene (D) [3 unique carbons] from the cis- and trans-2-butenes (B) and (C) [each with 2 unique
carbons]. Thus, butene 1 must be isobutylene (D), which shows three unique carbons in its proton-decoupled 13C
NMR spectrum. Similarly, butene 2 must be 1-butene (A), which shows four unique carbons in its protondecoupled 13C NMR spectrum. (Chemical shift assignments are not required for full credit.)
18
25.8
134.3
141.8
25.8
112.1
116.4
14.0
26.7
1 (= D)
2 (= A)
(b) (3 pts) Deduce the structure of dibromide 3. Draw your proposed structure for dibromide 3, and label the hydrogens
on your proposed structure. Support your structural assignment by assigning the 1H NMR signals to the appropriate
hydrogens.
a
Br
PyHBr3
1
CH2Cl2
0 C
Br
Note: The relative integrals need to be multiplied by a factor of two to give the absolute integrals.
(c) You should be able to deduce the structure of dibromide 4, based on your proposed structure of butene 2. (There are
no rearrangements here THINK SIMPLE!) Of course, we eventually want you to assign all of the 1H NMR signals for
dibromide 4 and to explain the splitting patterns. However, we suspect that you may find the 1H NMR spectrum of
dibromide 4 more complicated than expected. So, a little guidance is in order. (Hint: Chemical shift calculations are not
required, but may prove helpful for your spectral analyses.)
(1) (1 pt) Draw the structure for dibromide 4, based on your proposed structure for butene 2.
Br
3
2
Br
This bromination reaction produces a racemic mixture of 1,2-dibromobutane (4). The 1H NMR spectral
complications are a result of the newly created stereogenic center at C-2. The chemical shift calculations (not
required) are summarized below:
#
#
#
#
(2) (10 pts) Draw the lowest energy staggered Newman projection looking down the carbon-carbon bond, connecting
the two bromine-substituted carbon atoms of dibromide 4. Label the hydrogens on these two carbon atoms. Now,
assign the 1H NMR signals to these labeled hydrogens and explain the observed splitting patterns. Does the magnitude
of the observed coupling constants support your lowest energy conformational assignment? Explain.
Br
Et
! 4.10-4.20 Hc
Ha ! 3.63
! 3.84 Hb
Br
4
19
The methylene protons at C-1 (Ha and Hb) are diastereotopic. Even though there is free rotation about the C-1/C-2
bond, these methylene protons are not equivalent, as nicely illustrated by the Newman projection of the most
populated (lowest energy) staggered conformation (looking down the C-1/C-2 bond), shown above, for one
enantiomer of 4. As you learned in lab, the lowest energy conformation here keeps the two bromine atoms as far
apart as possible to minimize any Br/Br dipole destabilization. The 1H NMR signal at # 3.63 ppm is due to Ha. This
signal appears at as a triplet because the two coupling constants are approximately equal (Jab ~ Jac = 10 Hz). Jab is
large, of course, because the two protons are geminally coupled. The large vicinal coupling constant (Jac = 10 Hz) is
consistent with a large dihedral angle (~180) for Ha-C-C-Hc. The 1H NMR signal at # 3.84 ppm is due to Hb. This
signal appears as a doublet of doublets with Jab = 10 Hz and Jbc = 4.5 Hz. Again, Jab is large because it is a geminal
coupling constant. The smaller vicinal coupling constant (Jbc = 4.5 Hz) is consistent with a smaller dihedral angle
(~60) for Hb-C-C-Hc. Finally, the multiplet at # 4.10-4.20 ppm is due to Hc. Thus far, Hc should be a dd with Jac =
10 Hz and Jbc = 4.5 Hz. However, as we shall see, Hc is split by two additional protons and will be more complicated
than a dd.
(3) (4 pts) Please explain why the multiplets at d 1.75-1.91 and 2.12-2.26 ppm appear as separate 1H multiplets,
rather than as one 2H multiplet. Which two protons in dibromide 4 give rise to these two multiplets?
The 1H multiplets at # 1.75-1.91 and 2.12-2.26 ppm are due to the C-3 methylene protons (Hd and He). These
methylene protons are also diastereotopic due to the C-2 stereogenic center. This situation can nicely be illustrated
by examining the lowest energy staggered Newman projection, looking down the C-3/C-2 bond, shown below.
CH3
Br
! 4.10-4.20 Hc
Hd ! 1.75-1.91 or 2.12-2.26
! 1.75-1.91 or 2.12-2.26 He
CH2Br
4
Alternately, you can demonstrate the diastereotopicity of Hd and He by performing the X substitution test; i.e.,
"X substn."
H3C
Hc
Br
He
X
H3C
Hc
Br
Diastereomers!
He
Hd
CH2Br
CH2Br
"X substn."
H3C
Hc
Br
X
Hd
CH2Br
You dont have enough information to assign which proton is which here, as both signals were only reported as
multiplets. Hd should be a ddq (Jde, Jcd, and Jdf), which could be reduced to a tq, if Jde ~ Jcd. He should be a dqd (Jde,
Jdf, and Jce).
(4) (2 pts) Please assign the remaining signal in the 1H NMR spectrum of dibromide 4, and explain the observed
splitting pattern. Dont forget the label(s).
The remaining signal in the 1H NMR spectrum of dibromide 4 is the 3H triplet at # 1.08 ppm. This signal must be
due to the C-4 methyl group (Hf). The signal appears as a triplet because the methyl protons are coupled to Hd and
20
He with Jdf ~ Jef ~ 7 Hz (due to rotational averaging). Note that coupling constant for the methyl hydrogens (Hf)
with Hd and He must both be 7 Hz; otherwise, the methyl signal would appear as a dd.
(5) (2 pts) The signal at # 4.10-4.20 ppm is reported simply as a multiplet (m), although perhaps mess might be a
more apt description. The proton, giving rise to this mutiplet, should already be labeled in your Newman Projection
from Part 2 above. What should be the actual multiplicity of this signal (e.g., dd, td, etc.)? Explain.
The signal at # 4.10-4.20 ppm has presumably already been assigned to the C-2 methine proton (Hc). This proton is
coupled to four different protons (Ha, Hb, Hd, and He) with four different coupling constants (Jac, Jbc, Jcd, and Jce).
Thus, Hc should actually appear as a doublet of doublets of doublets of doublets (dddd) with 16 lines (assuming
none of the lines overlap, which is unlikely).
21
Ph = phenyl
t-Bu = tert-butyl
THF
Me
Me
LDA = lithium disopropylamide
Li
N
Me
Me
Ts = tosylate =
Me
O
O
DMSO
Me
O
DMF
Me
NMe2
22